Comparative Effects of Bone Marrow-derived Versus Umbilical Cord Tissue Mesenchymal Stem Cells in an Experimental Model of Bronchopulmonary Dysplasia

Merline Benny, Benjamin Courchia, Sebastian Shrager, Mayank Sharma, Pingping Chen, Joanne Duara, Krystalenia Valasaki, Michael A. Bellio, Andreas Damianos, Jian Huang, Ronald Zambrano, Augusto Schmidt, Shu Wu, Omaida C. Velazquez, Joshua M. Hare, Aisha Khan, Karen C. Young

Research output: Contribution to journalArticlepeer-review

Abstract

Bronchopulmonary dysplasia (BPD) is a life-threatening condition in preterm infants with few effective therapies. Mesenchymal stem or stromal cells (MSCs) are a promising therapeutic strategy for BPD. The ideal MSC source for BPD prevention is however unknown. The objective of this study was to compare the regenerative effects of MSC obtained from bone marrow (BM) and umbilical cord tissue (UCT) in an experimental BPD model. In vitro, UCT-MSC demonstrated greater proliferation and expression of anti-inflammatory cytokines as compared to BM-MSC. Lung epithelial cells incubated with UCT-MSC conditioned media (CM) had better-wound healing following scratch injury. UCT-MSC CM and BM-MSC CM had similar pro-angiogenic effects on hyperoxia-exposed pulmonary microvascular endothelial cells. In vivo, newborn rats exposed to normoxia or hyperoxia (85% O2) from postnatal day (P) 1 to 21 were given intra-tracheal (IT) BM or UCT-MSC (1 × 106 cells/50 μL), or placebo (PL) on P3. Hyperoxia PL-treated rats had marked alveolar simplification, reduced lung vascular density, pulmonary vascular remodeling, and lung inflammation. In contrast, administration of both BM-MSC and UCT-MSC significantly improved alveolar structure, lung angiogenesis, pulmonary vascular remodeling, and lung inflammation. UCT-MSC hyperoxia-exposed rats however had greater improvement in some morphometric measures of alveolarization and less lung macrophage infiltration as compared to the BM-MSC-treated group. Together, these findings suggest that BM-MSC and UCT-MSC have significant lung regenerative effects in experimental BPD but UCT-MSC suppresses lung macrophage infiltration and promotes lung epithelial cell healing to a greater degree.

Original languageEnglish (US)
Pages (from-to)189-199
Number of pages11
JournalStem Cells Translational Medicine
Volume11
Issue number2
DOIs
StatePublished - Mar 17 2022

Keywords

  • bone marrow
  • bronchopulmonary dysplasia
  • cell therapy
  • mesenchymal stem cells
  • umbilical cord tissue

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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